title: Narrow escape for a stochastically gated Brownian ligand.
abstract: Molecular activation in cellular microdomains is usually characterized by a forward binding rate, which is the reciprocal of the arrival time of a ligand to a key target. Upon chemical interactions or conformational changes, a Brownian ligand may randomly switch between different states, and when target activation is possible in a specific state only, switching can significantly alter the activation process. The main goal of this paper is to study the mean time for a switching ligand to activate a small substrate, modelled as the time to exit a microdomain through a small absorbing window on the surface. We present the equations for the mean sojourn times the ligand spends in each state, and study the escape process with switching between two states in dimension one and three. When the ligand can exit in only one of the two states, we find that switching always decreases its sojourn time in the state where it can exit. Moreover, the fastest exit is obtained when the ligand diffuses most of the time in the state with the maximal diffusion coefficient, although this may imply that it spends most of the time 'hidden' in the state where it cannot exit. We discuss the physical mechanisms responsible for this apparent paradox. In dimension three we confirm our results with Brownian simulations. Finally, we suggest possible applications in cellular biology.
authors.affiliation: Department of Computational Biology, Ecole Normale Supérieure, 46 rue d'Ulm, 75005 Paris, France.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Reingruber
authors.forename: David
authors.initials: D
authors.lastname: Holcman
mesh_terms: D000042:Absorption; D001703:Biophysics / Q000379:methods*; D003585:Cell Biology; D004058:Diffusion; D007700:Kinetics; D008024:Ligands; D015233:Models, Statistical; D008968:Molecular Conformation; D016011:Normal Distribution; D016012:Poisson Distribution; D013997:Time Factors
chemical_list: D008024:Ligands